Mouse class II transactivator: cDNA sequence and amino acid comparison with the human class II transactivator

CIITA is a major histocompatibility complex (MHC) class II transcription regulator in both human and mouse. It does not bind DNA but rather functions through the transactivation of a conserved set of DNA binding proteins in the class II promoter region. Previous work has shown that induction of cell surface MHC class II molecules by interferon- gamma (IFN- gamma ) is accompanied by an increase in the steady state class II mRNA levels and that this is largely due to an increase in the rate of transcription. Humans born without CIITA lack basal and inducible class II expression and suffer a form of combined immunodeficiency but display no other abnormalities. Similar abnormalities occur in mice with disrupted CIITA genes, indicating that CIITA is essential for the regulation of class II in the normal immune response. HLA-DR, -DP, -DQ, -DM alpha , -DM beta , and the invariant chain have been shown to be activated by CIITA. Therefore CIITA is a global regulator of antigen presentation to CD4 T cells. The human CIITA cDNA is 4543 base pairs (bp) in length with an open reading frame of 3390 bp, coding for a predicted protein of 1130 amino acids (aa). The carboxy-terminal region of CIITA is thought to be responsible for class II transcription specificity, while the amino-terminal acidic region likely binds non-specific transcription factors. If these regions are important for MHC class II induction, it is hypothesized that they will be highly conserved in mouse and man, but the full-length mouse cDNA sequence has yet to be described.